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TM The Feline Centre Langford and working together for the benefit of cats Beginner’s GUIDE TO USING GENETIC TESTS IN CATS Chris Helps BSc (hons) PhD. Senior Research Fellow and Head of the Molecular Diagnostic Unit, Langford. BACKGROUND Just like any other mammalian species, including man, cats suffer from genetic diseases and have traits controlled by genetic mutations. Fig. 1: An example of a familial inherited defect of which a genetic Whilst considerably more is known about human test has become available - episodic hypokalaemic polymyopathy, genetics, there have been major advances in our most often seen in Burmese and related breeds. This Burmese cat understanding of feline genetics over recent years. shows ventral neck flexion which is indicative of muscle weakness. As in humans, the feline genome has been and carrier cats never show any signs of the disease. sequenced (although there is still more work to The ability to determine the genetic status of these cats be done in identifying all of the genes) and this has before they are of breeding age significantly helps cat greatly helped the discovery of genetic mutations. breeders to manage and plan their breeding programmes The ability to determine whether a cat is likely to suffer so they do not produce affected kittens. from a genetic disease by just taking and analysing a mouth swab has been of benefit to both disease diagnosis AVAILABLE TESTS and breeding strategies. For example, before the genetic Over recent years, many genetic tests for cats have mutation responsible for polycystic kidney disease was become available (see Table 1). These cover a range of discovered in 2004, the disease could only be diagnosed genetic conditions including diseases, coat colours and ante-mortem by ultrasound scanning of the kidneys. blood type. Some genetic mutations appear to be Whilst this was a reliable diagnostic technique, it could distributed throughout many breeds of cat (e.g. the coat not be undertaken until the cat was at least 10 months of colour mutations), whilst others are specific to only single age, required the cat to be brought to the clinic and cat breeds (e.g. Ragdoll hypertrophic cardiomyopathy). It needed specialist equipment and operators. With genetic is important to bear this in mind when requesting certain testing, a diagnosis can be made from a mouth swab taken genetic tests on certain breeds of cat, since although the from the cat by a vet or breeder and sent to a testing test can be run and a result obtained, the result may not laboratory; in addition the swab can be taken from cats of be relevant to disease in that breed. Testing laboratories any age. Samples are not normally accepted directly from are always happy to discuss breed/test combinations if owners, however, the advent of owner-submitted swabs veterinary surgeons are unsure of their validity. Another for genetic testing is primarily used to inform breeding issue to bear in mind is that certain cat breeds are allowed strategies rather than decisions regarding the health and to use other breeds in outcross programmes, which welfare of individual cats. For cases that involve diagnosis, means that some of the more breed specific mutations treatment or ongoing monitoring we would still recommend may start arising in other breeds if the outcross cats have veterinary involvement. This revolution is even more not been tested. Researchers at Langford are continually important for genetic diseases that have a late-onset and/ working to find new mutations responsible for other feline or are inherited in a recessive manner, e.g. retinal atrophy. genetic diseases and traits and due to the considerable Because clinical signs often do not appear until at least 3-5 amount of work this involves often participate in years of age, affected cats may have been used for international studies, such as was the case recently with breeding extensively before they show clinical signs of disease episodic hypokalaemic polymyopathy (Fig. 1). www.felineupdate.co.uk 1 Beginner’s guide to using GENETIC TESTS IN CATS GENETIC TEST BREEDS KNOWN TO HAVE THE MUTATION Ragdoll hypertrophic cardiomyopathy Ragdoll, Ragamuffin Maine Coon hypertrophic cardiomyopathy Maine Coon Polycystic kidney disease Persian, Chinchillas, Exotics, BSH, Ragdoll, Birmans, Asians, Cornish Rex, Devon Rex, Snowshoes Pyruvate kinase deficiency Abyssinian, Somali, Bengal, Singapura, Egyptian Mau, La Perm, Maine Coon, Norwegian Forest Cat, Savannah, Siberian Progressive retinal atrophy Abyssinian, Somali, Ocicat, Siamese, Balinese/Javanese, Oriental Shorthair, Colourpoint Shorthair Blood type Any Chocolate coat colour Any Cinnamon coat colour Any Dilute coat colour Any Agouti coat colour Any ALC Agouti colour Bengal Siamese colourpoint Any Burmese colouration Any Long hair/Short hair M1 found in Ragdoll M2 found in Norwegian Forest Cat and Tiffanie M3 found in Ragdoll and Maine Coon M4 found in all breeds including the above Glycogen storage disease type IV Norwegian Forest Cat Amber coat colour Norwegian Forest Cat Gangliosidosis (GM2) Burmese Episodic hypokalaemic polymyopathy Burmese, Asian, Australian Mist, Bombay, Burmilla, Cornish Rex, Devon Rex, Singapura, Sphinx, Tiffanie, Tonkinese Spinal muscular atrophy Maine Coon Table 1: Feline genetic tests available at Langford Veterinary Services www.catgenetics.co.uk SAMPLES In the early days of genetic testing, a blood sample was still worth reiterating that the aim of a mouth swab is required to obtain an adequate amount cat DNA. to collect cheek cells, which contain the DNA, and not Technological improvements mean we can now to collect just saliva. It is also important that swabs routinely use mouth swabs, which are less invasive and are taken at least an hour after cats and kittens have can be taken by the breeder, although blood samples fed. The swab tip is inserted between cheek and gum will still work fine. The vast majority of the ~6000 and twirled for a few seconds, ideally this should be samples a year that we analyse are mouth swabs repeated on the other side of the cat’s mouth. Breeders submitted by owners and breeders. are encouraged to swab cats one at a time to reduce the The quality of the mouth swab is of vital importance risk of mixing up the swabs and keep swabs separate to for reliable and accurate genetic testing, and in our prevent cross contamination. Swabs should be sent to experience the swabs that breeders collect are the laboratory as soon as possible since bacteria and satisfactory more than 98% of the time. However, it is fungi can grow on them if they are stored for too long. www.felineupdate.co.uk 2 Beginner’s guide to using GENETIC TESTS IN CATS SUBMISSION All genetic testing laboratories now accept direct genetic and environmental factors, such as other submission of mouth swabs from owners and breeders, genetic mutations that may have a protective as well as mouth swabs and/or blood samples from effect, the effect of diet etc. veterinary surgeons. The main aim of breeders who submit samples is not to determine disease status, but rather to inform their breeding programme, e.g. so that they do not mate two cats carrying a recessive genetic disease. In some circumstances (see below) there is a requirement for the veterinary surgeon to collect the mouth swab and confirm the cat’s identity by its microchip number: n International Cat Care (formerly Feline Advisory Bureau) run various negative registers for genetic diseases (e.g. polycystic kidney disease and hypertrophic cardiomyopathy) that require the cat’s identity to be confirmed by a veterinary surgeon. n The Governing Council of the Cat Fancy (GCCF) run various Active registers (e.g. Ragdoll hypertrophic Fig. 2: Ultrasound image (courtesy of Kate Bradley) cardiomyopathy) that require the cat’s identity to showing multiple cysts within a kidney of a Persian cat be confirmed by a veterinary surgeon. affected by polycystic kidney disease. LABORATORY When swabs arrive at the Langford, the DNA is extracted from the cheek cells and polymerase chain reaction (PCR) is used to copy a short section of DNA containing the genetic mutation millions of times. The DNA sequence surrounding the mutation is then determined by pyrosequencing, which is used to indicate whether the cat has the mutation, and if it does, whether it is a carrier. Turnaround time for genetic testing at Langford is 3-4 days. INTERPRETATION Interpretation of genetic test results, especially those Fig. 3: Gross pathology of kidneys at post mortem from a for genetic diseases, can cause issues for both breeders and veterinary surgeons for several reasons: Persian cat affected by polycystic kidney disease. n The absence of a mutation known to cause a genetic n Some genetic disease mutations appear to have disease does not mean the cat can never suffer from greater penetrance than others. For example, cats that disease; it only means that the known mutation with the PKD mutation will invariably develop cystic is not responsible for the disease. There are kidneys at some point in their lives (Figs. 2 & 3). therefore limitations to using genetic tests for However, cats homozygous for the known HCM diagnosis of a particular condition. For example, mutations do not necessarily show phenotypic the mutation that is known to cause hypertrophic effects. Those that do often have very variable cardiomyopathy (HCM), in Maine Coon cats is not outcomes, with some dying at an early age and the only factor involved in HCM due to the fact that others living much longer. some Maine Coon cats suffering HCM do not have n A genetic mutation normally found in one breed of that particular mutation. There may potentially be cat (e.g. pyruvate kinase deficiency), may or may multiple mutations that play a part in the condition not be of concern when discovered in other breeds.

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